Eluteaduste valdkonna intellektuaalse omandi kaitse
Patendiotsing, patendinõudlus
Margus Sarap, Euroopa patendivolinik
17.aprill 2013, Tartu Biotehnoloogia Park

Biotehnoloogia erisused?
4/2/2013 2Margus Sarap, 2013

Mittepatenditavad:
bioloogilisi meetodeid
bioloogilise aine, taime või looma
saamiseks
välja arvatud mikrobioloogilised meetodid
mikroorganismide saamiseks
leiutised, mida saab kasutada ainult ühe
kindla taimesordi või loomatõu puhul
NB! Bioloogilise aine, taime või looma
saamise olemuselt bioloogiline meetod
on meetod, mis täielikult põhineb
looduslikul nähtusel, nagu ristamine ja
selektsioon.
Biotehnoloogia erisused?
4/2/2013 3Margus Sarap, 2013

NB!
Ühe ja sama patenditaotlusega saab
taotleda patendikaitset ainult ühele
leiutisele või ühtse leiundusliku mõttega
seotud leiutiste kombinatsioonile
Biotehnoloogia erisused?
4/2/2013 4Margus Sarap, 2013

Biotehnoloogia erisused?
1. A fluorescent probe for determining protein kinase activity with the general formula
(I):
(X-Y-Z)-L-F (I),
wherein
X-Y-Z is a bisubstrate-analog inhibitor of a protein kinase, in which X is a
compound that binds to the ATP-binding pocket of the kinase and;
Z is a compound that binds to the protein/peptide-binding domain of the
kinase;
Y is a an organic tether that connects X and Z and permits simultaneous binding
of X and Z to the active site of the kinase;
F is a fluorescent dye which optical characteristics are changed in the course of
the binding of (X-Y-Z)-L-F to the kinase;
L is a linker (between the bisubstrate-analog inhibitor XYZ and fluorescent label
F) formed of a hydrocarbon chain, of other type of organic molecule or of part of
organic molecule; may be omitted in the probe and F directly bound to inhibitor XYZ.
4/2/2013 5Margus Sarap, 2013

Biotehnoloogia erisused?
1. A fluorescent probe for a protein kinase selected from the group consisting of:
2. A kit comprising a fluorescent probe of claim 1.
3. A bisubstrate-analog inhibitor of a basophilic protein kinase selected from the group
consisting of:
4. A method for determining the fraction of an active binding form of a protein kinase in
a sample containing a fluorescent probe of claim 1 ...
N
O
N
N
OHOH
N
NH2
O
N
O
N
+
-OOC
O
NH
O
NH-(D-Arg)6
-(D-Lys)-C(=O)-NH2
NH
N
S OO
HN
N
H
O
NH-(D-Arg)6-D-Lys(5-TAMRA)-C(O)NH2 N
O
N
N
OHOH
N
NH2
O
O
NH-(D-Arg)6-(D-Lys)-C(=O)-NH2
N
NO
O2
N
N
H
NH
N
O
N
N
OHOH
N
NH2
O
N
O
N
+
-OOC
O
NH
O
NH-(D-Arg)6
-(D-Lys)-C(=O)-NH2
NH
N
S OO
HN
N
H
O
NH-(D-Arg)6-D-Lys(5-TAMRA)-C(O)NH2 N
O
N
N
OHOH
N
NH2
O
O
NH-(D-Arg)6-(D-Lys)-C(=O)-NH2
N
NO
O2
N
N
H
NH
4/2/2013 6Margus Sarap, 2013
patent US8,158,376

Patendidokumendi ülesehitus?
•Leiutiskirjeldus – specification
–Pealkiri - Title
–Tehnika valdkond – Technical Field
–Tehnika tase – Background Art
–Leiutise olemus – Summary of invention
–Jooniste loetelu – Brief description od drawings
–Teostusnäi(de)ted – Description of embodiments
–Viited – Recitation list
–Patendinõudlus - Claims
–Lühikokkuvõte - Abstract
–Joonised - Drawings
9.12.2011 7Sarap ja Partnerid, ©2011

Patendidokumendi erinevate osade tähendu
Kõige tähtsam – patendinõudlus
tehnilise lahenduse (leiutise) kaitseulatus
sõltumatu punkt
sõltuvad punktid
9.12.2011 8Sarap ja Partnerid, ©2011

Patendidokumendi erinevate osade tähendus?
Leiutiskirjeldus
leiutise olemuse avamine
tehnilise lahenduse täpne kirjeldus
9.12.2011 9Sarap ja Partnerid, ©2011

Vähiravi
Explanation of terms
•Heat shock protein 90 (HSP 90)
Belongs to a class of proteins that protect cells
when stressed by elevated temperatures;
assists in tumour repression.
•Heat shock protein 90 inhibitor (HSP 90
inhibitor)
Compounds which block the functioning of HSP
90. Examples: geldanamycin or 17-alkylamino-
17-desmethoxygeldanamycin (17-AAG).
•Platinum coordination complexes
Platinum complexed with ligands. These
compounds are used as chemotherapeutics.
Examples: cisplatin, carboplatin, oxaliplatin.
17-AAG, R17 = alkylamino
Oxaliplatin
Allikas EPO materjalid , nõudluse tõlgendamine

Leiutis
An improved way of treating people suffering from
breast cancer
by injecting a platinum coordination complex and
optionally
also an HSP 90 inhibitor.
The invention shows improved results by combining
the two compounds. The specific combination of
oxaliplatin and 17-AAG has a synergistic effect.
How can you protect it from imitation?
• "An improved way" → Compared with what? (term not
clear)
• "Way of treating people" → Method of treatment of the human or
animal body by therapy = excluded
from patentability
• "A platinum coordination → Not a "method of treatment"; has a
complex " technical function → possible patent
Allikas EPO materjalid , nõudluse tõlgendamine

Patent Claim: "A platinum coordination complex"
How to patent this invention: claim it!
Claiming a platinum coordination complex in general means trying to get
very broad protection. You already know that such complexes have been
described before.
Patent Claim: "A platinum coordination complex for use in the treatment of
suffering people."
This wording also does not describe what you invented.
Patent Claim: "A platinum coordination complex for use in the treatment of
breast cancer."
A prior art search will show whether the invention
– as claimed – is actually new.
Allikas EPO materjalid , nõudluse tõlgendamine

Tehnika taseme otsingu tulemused
The prior art search found a journal article that discloses the invention.
Cancer Treatment Reports 67(3) 235-238, 1983
"... 2 [patients] with adrenocarcinomas in the breast ... were treated
with cisplatin at a dose of 60 mg/m2 ..."
A platinum coordination complex (i.e. cisplatin) for use in the treatment
of cancer is already known from this journal article!
Allikas EPO materjalid , nõudluse tõlgendamine

Comparison of the two inventions
The invention
as claimed
Cancer Treatment Reports
"A platinum coordination
complex for use in the
treatment of breast cancer."
"... 2 [patients] with
adrenocarcinomas in the
breast ... were treated
with cisplatin at a dose of 60
mg/m2
..."
"A combination of a platinum
coordination complex and an
HSP 90 inhibitor for use ..."
• New
• Inventive step
(the combined use shows
improved effects)
Allikas EPO materjalid , nõudluse tõlgendamine
Not new

Leiutist kaitsev nõudlus
Claim to be filed:
"A combination of a platinum coordination complex and
an HSP 90 inhibitor for use in the treatment of breast
cancer."
Allikas EPO materjalid , nõudluse tõlgendamine

Sõltumatute nõudluste kasutamine kaitse
täiendamiseks
The patent should include both broad and specific claims.
Broad:
An independent claim (i.e. a claim
stating the essential features of
the invention) helps prevent the
patent from being circumvented.
Specific:
Dependent claims refer to an
independent claim and
additionally define preferred
embodiments of the invention.
Independent claim
Dependent claim 1
Dependent claim 2
Allikas EPO materjalid , nõudluse tõlgendamine

Patendiametile (EPO) esitatud taotlus
CLAIM 1:
"A combination of a platinum coordination complex and an HSP 90
inhibitor for use in the treatment of breast cancer."
Claim 2: "A combination according to claim 1, characterised
in that the HSP 90 inhibitor is 17-AAG."
Claim 3: "A combination according to claim 1, characterised
in that the platinum coordination complex is oxaliplatin."
The patent office will perform its own prior art search and then
consider whether the invention AS CLAIMED is new and non-obvious.
Claim 4: "A combination according to claim 2, characterised
in that the platinum coordination complex is oxaliplatin."
Allikas EPO materjalid , nõudluse tõlgendamine

Tehnika tase EPO otsingust
"Combination of HSP 90 inhibitor ... with anticancer agents
like carboplatin or cisplatin ... to inhibit ... growth of breast
cancer cells."
"Methods for enhancing the efficacy of cytotoxic agents through
the use of HSP90 inhibitors"

EPO arvamus
Applicant's claim:
"A combination of a platinum
coordination complex and an HSP 90
inhibitor for use in the treatment of
breast cancer."
The invention according to claim 1
is already shown and claimed in
WO 02/15925.
EPO response:
Please amend your claims if you want your invention patented!
A platinum coordination complex
(e.g. cisplatin) and an HSP 90
inhibitor were used in
WO 02/15925 to treat breast
cancer.

Edasine analüüs
•Check the material revealed in the prior art searches:
• Does the invention have any features NOT disclosed in the
prior art?
• What are the advantages of the invention compared with
the prior art?
How can the claims be amended to reflect the invention
in a way that it is new (considering all the prior art)?
•Did the EPO interpret any important features of the
invention differently to the inventor?
Applicant's reply: amendments to the application,
explanation of the relationship between the invention
and the prior art

Synergism (more than additive)
Claim 2: Features of Claim 1 +
HSP90 inhibitor = 17-AAG
Claim 4: Features of Claims 1 + 2 +
Pt coordination complex = oxaliplatin
Cancer Treatment
Reports
Improved effect (additive)
Claim 3: Features of Claim 1 +
Pt coordination complex = oxaliplatin
Claim 1: Combination of HSP 90
inhibitor and Pt coordination complex
Leiutise võrdlus tehnika tasemega
Technical features of the invention
WO 02/15925
Advantages/technical result
No
No
No No
No
No
No
No
No
No

Analüüsi tulemus
Although the individual elements of the invention are known, the
combination of specific compounds is not and it produces a new, unique
benefit. But you have to take into account that:
Claim 2 refers to the use of 17-AAG. To use this specific HSP 90 inhibitor is
considered to be trivial, because WO 02/15925 recommends using any
HSP 90 inhibitor in combination with an anticancer agent.
Claim 3 teaches the use of oxaliplatin. Again, since WO 02/15925 hints at
the use of any anticancer drug, the use of oxaliplatin is also considered to
be obvious.
Claim 4 describes the use of the combination of oxaliplatin and 17-AAG.
It is shown in the patent application that the combination produces a
synergistic (= more than additive) effect. This is not disclosed in
WO 02/15925.

Analüüsi tulemused
If one compound is simply replaced by another without showing any
unexpected or surprising effect, such a replacement is frequently
considered to represent routine for an expert.
If an unexpected or surprising effect can be shown, then the invention is
often considered to be inventive (i.e. the invention is not obvious for an
expert working in the technical field).
The use of 17-AAG and oxaliplatin, which leads to an unexpected
synergistic combination, is therefore inventive.
Invention
(new + inventive)
R17 = alkylamino

The present invention provides a method for treating cancer. The
method involves the administration of an HSP90 inhibitor and a
platinum coordination complex, where the combined administration
provides a synergistic effect.
The HSP90 inhibitor for this aspect is typically 17-AAG, while the
platinum coordination complex is oxaliplatin.
17-AAG combination in SKSBr-3 cells [0093] The following table
provides CI values for combinations of 17-AAG and the platinum
complexes oxaliplatin and cisplatin in an SKBr-3 cell assay ...
EPOsse esitatud kirjeldus toetab parandusi
Different
to "Cancer
Treatment
…"
Different
to patent
WO02/…
Supports
inventive
step:
different
technical
result

Väljaantud patendi nõudlus
Claim 1 as granted reads:
"Medicament comprising 17-Alkylamino-17-desmethoxygeldanamycin
(17-AAG) and oxaliplatin for use in the treatment of breast cancer
in a patient."
Response from EPO: granted!

EP1179050
•1. A method for removal of protein kinase from a liquid
containing the protein kinase by contacting the liquid with a
carrier bound affinity ligand for the kinase, characterized in that
the ligand is a bisubstrate inhibitor for the kinase whereas the
ligand is attached to the carrier.
•2. The method of claim 1, characterized in that the bisubstrate
inhibitor comprises the structure
•C-(L) n-N
•where
•(a) C contains a structure inhibiting binding of the
peptide/protein substrate to the protein kinase,
•(b) L is an organic linker,
•(c) n is an integer 0 or 1, and
•(d) N is an inhibitor competitively inhibiting binding of the
nucleoside triphosphate (NTP) to the protein kinase;
•and the structure is attached to the carrier via C.
•3. The method of any one of claims 1-2, characterized in that C is
a peptide substrate consensus sequence or a pseudosubstrate
consensus sequence.4/2/2013 Margus Sarap, 2013 26

Näide
4/2/2013 Margus Sarap, 2013 27
• 1. A method for removal of protein kinase from a liquid containing the
protein kinase by contacting the liquid with a carrier bound affinity ligand
for the kinase, characterized in that the affinity ligand is a bisubstrate
inhibitor having a structure containing
• - a moiety having the structure that is able to competitively inhibit binding
of the relevant nucleotide triphosphate (NTP) and
• - a moiety having the structure that is able to competitively inhibit binding
of peptide or protein substrate
• to the particular protein kinase molecule whereas the ligand is attached to
the carrier.
• 2. The method of claim 1, characterized in that the bisubstrate inhibitor
for the particular protein kinase molecule comprises the structure
• C-(L) n-N
• where
• (a) C contains a structure inhibiting binding of the peptide or protein
substrate to the protein kinase,
• (b) L is an organic linker,
• (c) n is an integer 0 or 1, and
• (d) N is an inhibitor competitively inhibiting binding of the nucleoside
triphosphate (NTP) to the protein kinase.
• 3. The method of any one of claims 1-2, characterized in that C is a peptide
substrate consensus sequence or a pseudosubstrate consensus sequence.

• 1. A method for removal of protein kinase from a liquid containing the protein
kinase by contacting the liquid with an affinity ligand for the kinase bound to a
carrier insoluble in aqueous media, characterized in that the affinity ligand is a
bisubstrate inhibitor having a structure containing simultaneously
• - a moiety having the structure that is able to competitively inhibit binding of the
relevant nucleotide triphosphate (NTP) and
• - a non-phosphorylatable moiety having the structure that is able to competitively
inhibit binding of peptide or protein substrate
• whereas both moieties target the particular protein kinase molecule whereas the
ligand is attached to the carrier.
• 2. The method of claim 1, characterized in that the bisubstrate inhibitor for the
particular protein kinase molecule comprises the structure
• C-(L)n-N
• where
• (a) C contains a structure inhibiting binding of the peptide or protein substrate to
the protein kinase,
• (b) L is an organic linker,
• (c) n is an integer 0 or 1, and
• (d) N is an inhibitor competitively inhibiting binding of the nucleoside triphosphate
(NTP) to the protein kinase.
• 3. The method of any one of claims 1-2, characterized in that C is a peptide substrate
consensus sequence or a pseudosubstrate consensus sequence.
4/2/2013 Margus Sarap, 2013 28

4/2/2013 Margus Sarap, 2013 29
Claims
1. A method for removal of protein kinase from a liquid containing the protein kinase by
contacting the liquid with an affinity ligand for the kinase bound to a carrier insoluble in
aqueous media characterized in that the affinity ligand is a bisubstrate inhibitor having a
structure containing simultaneously
- a moiety having the structure that is able to competitively inhibit binding of the relevant
nucleotide triphosphate (NTP) and
- a non-phosphorylatable moiety having the structure that is able to competitively inhibit
binding of peptide or
protein substrate whereas both moieties target the particular protein kinase molecule whereas
the ligand is attached to the carrier.
2. The method of claim 1, characterized in that the bisubstrate inhibitor for the particular
protein kinase molecule comprises the structure
C-(L)n-N
where
(a) C contains a structure inhibiting binding of the peptide or protein substrate to the protein
kinase,
(b) L is an organic linker,
(c) n is an integer 0 or 1, and
(d) N is an inhibitor competitively inhibiting binding of the nucleoside triphosphate (NTP) to
the protein kinase.
3. The method of any one of claim 2, characterized in that C is a peptide substrate consensus
sequence or a pseudosubstrate consensus sequence.

Nõudlused kellele
•taotleja -> võimalikult lai kaitse
•Patendiameti ekspert -> tehnika tase -> kitsendamine
•konkurent
• patendi vaidlustamine’
• rikkumine
•rikkuja
4/2/2013 Margus Sarap, 2013 30

EE03157
•1. Optiliselt puhas ühend, mida iseloomustab see,
et ühend on (-)-5-metoksü-2-{[(4-metoksü-3,5-
dimetüül-2-püridinüül)metüül]sulfinüül]-H-
bensimidasooli Na+
-, Mg2+
-, Li+
-, K+
- Ca2+
- või N+
(R)4-
sool, milles R on alküülrühm 1-4
süsinikuaatomiga.
4/2/2013 Margus Sarap, 2013 31
Küsimused?
-Mis on optilise puhtuse määr
-tehnika tasemest tuntud Na, Mg soolad

Küsimused?
Sarap ja Partnerid
Patendibüroo
Margus Sarap
patent@patent.ee
tel 747 7058
Kompanii 1c, Tartu
Mikk Putk
mikk.putk@patent.ee
tel 53 039 088
Soo 46, Tallinn
4/2/2013 32Margus Sarap, 2013
www.patent.ee